title: Can tyrosine kinase inhibitors be discontinued in patients with metastatic renal cell carcinoma and a complete response to treatment? A multicentre, retrospective analysis.
abstract: BACKGROUND
  Discontinuation of treatment with tyrosine kinase inhibitors (TKIs) and readministration in case of recurrence could improve quality of life (QoL) and reduce treatment costs for patients with metastatic renal cell carcinoma (mRCC) in which a complete remission (CR) is achieved by medical treatment alone or with additional resection of residual metastases.
  
  
  OBJECTIVE
  To evaluate whether TKIs can be discontinued in these selected patients with mRCC.
  
  
  METHODS
  A retrospective analysis of medical records and imaging studies was performed on all patients with mRCC treated with TKIs (n=266) in five institutions. Patients with a CR under TKI treatment alone or with additional metastasectomy of residual disease following a partial response (PR), in which TKIs were discontinued, were included in the analysis. Outcome criteria analysed were time to recurrence of previous metastases, occurrence of new metastases, symptomatic progression, improvement of adverse events, and response to reexposure to TKIs.
  
  
  METHODS
  Sunitinib 50mg/day for 4 wk on and 2 wk off, sorafenib 800mg/day.
  
  
  METHODS
  Response according to Response Evaluation Criteria in Solid Tumours (RECIST).
  
  
  CONCLUSIONS
  We identified 12 cases: 5 CRs with sunitinib, 1 CR with sorafenib, and 6 surgical CRs with sunitinib followed by residual metastasectomy. Side-effects subsided in all patients off treatment. At a median follow-up of 8.5 mo (range: 4-25) from TKI discontinuation, 7 of 12 patients remained without recurrence and 5 had recurrent disease, with new metastases in 3 cases. Median time to progression was 6 mo (range: 3-8). Readministration of TKI was effective in all cases. The study is limited by small numbers and retrospective design.
  
  
  CONCLUSIONS
  Discontinuation of TKI in patients with mRCC and CR carries the risk of progression with new metastases and potential complications. Further investigation in a larger cohort of patients is warranted before such an approach can be regarded as safe.
authors.affiliation: Department of Urology, Charité - Universitätsmedizin Berlin, Berlin, Germany. manfred.johannsen@charite.de
authors.forename: Manfred
authors.initials: M
authors.lastname: Johannsen
authors.forename: Anne
authors.initials: A
authors.lastname: Flörcken
authors.forename: Axel
authors.initials: A
authors.lastname: Bex
authors.forename: Jan
authors.initials: J
authors.lastname: Roigas
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ficarra
authors.forename: Christian
authors.initials: C
authors.lastname: Kloeters
authors.forename: Matthias
authors.initials: M
authors.lastname: Rief
authors.forename: Patrik
authors.initials: P
authors.lastname: Rogalla
authors.forename: Kurt
authors.initials: K
authors.lastname: Miller
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D001557:Benzenesulfonates / Q000008:administration & dosage; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000008:administration & dosage; D011758:Pyrroles / Q000008:administration & dosage; D012189:Retrospective Studies; D018570:Risk Assessment; D000077157:Sorafenib; D000077210:Sunitinib; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed / Q000379:methods; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D009536:Niacinamide; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases; D000077210:Sunitinib